Travere Therapeutics Announces FDA Accelerated Approval of FILSPARIᵀᴹ (sparsentan), the First and Only Non-immunosuppressive Therapy for the Reduction of Proteinuria in IgA Nephropathy
Travere Therapeutics, Inc. (Nasdaq: TVTX) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to FILSPARI™ (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.
This indication is granted under accelerated approval based on reduction in proteinuria. It has not been established whether FILSPARI slows kidney function decline in patients with IgAN. The continued approval of FILSPARI may be contingent upon confirmation of a clinical benefit in the ongoing Phase 3 PROTECT Study, which is designed to demonstrate whether FILSPARI slows kidney function decline. Topline results from the two-year confirmatory endpoints in the PROTECT Study are expected in the fourth quarter of 2023 and are intended to support traditional approval of FILSPARI.
FILSPARI, a once-daily oral medication is designed to selectively target two critical pathways in the disease progression of IgAN (endothelin-1 and angiotensin II), and is the first and only non-immunosuppressive therapy approved for the treatment of this condition. IgAN is a rare kidney disease (RKD) and a leading cause of kidney failure due to glomerular disease, affecting up to 150,000 people in the U.S., with approximately 30,000 to 50,000 of such patients estimated to be addressable under the indication approved via accelerated approval. The Company expects FILSPARI to be available beginning the week of February 27, 2023, and will be providing a comprehensive patient support program throughout the patient’s treatment journey.
“The accelerated approval of FILSPARI is a significant milestone on our path to advancing a transformative treatment for the IgA nephropathy community,” said Eric Dube, Ph.D., president and chief executive officer, Travere Therapeutics. “As a first-of-its-kind, non-immunosuppressive therapy, we believe FILSPARI has the potential to ultimately become the new standard of care for IgA nephropathy and offer hope to those living with this condition who until now have had few treatment options. We are grateful to the patients, caregivers, clinical trial investigators, healthcare providers, and advocates who have worked alongside us to develop this innovative first-in-class therapy.”
“Today’s approval of FILSPARI sets the stage for a new standard of care for IgA nephropathy patients. A high proportion of individuals diagnosed with this disease do not sufficiently respond to the historical standard treatment, which has been therapies that are not indicated for IgA nephropathy. These treatments include hypertension drugs such as angiotensin-receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors and systemic glucocorticoids. As a result, many patients have struggled to manage their disease and have progressed more quickly to kidney failure,” said Dr. Brad Rovin, MD, Medical Director at Ohio State University Center for Clinical Research Management, Director of the Division for Nephrology, and steering committee member for the PROTECT clinical trial. “The approval of this innovative treatment is founded in data from the largest head-to-head Phase 3 clinical trial in IgA nephropathy. It is exciting to see that adult patients who are at risk of rapid disease progression, many of whom have waited a very long time for a treatment like this, now have hope for a better future.”
The approval of FILSPARI, granted under the FDA’s accelerated approval pathway, is based on clinically meaningful and statistically significant improvements in proteinuria compared to an active comparator in the pivotal and ongoing Phase 3 PROTECT Study, the largest head-to-head interventional study to date in IgAN. The PROTECT Study is a global, randomized, multicenter, double-blind, active-controlled clinical trial evaluating the safety and efficacy of 400 mg of FILSPARI, compared to 300 mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite maximal tolerated ACE or ARB therapy.
In August 2021, the Company announced positive topline interim results that were based on the pre-specified, primary analyses set which showed that after 36 weeks of treatment, patients receiving FILSPARI achieved a mean reduction in proteinuria from baseline of 49.8%, compared to a mean reduction in proteinuria from baseline of 15.1% for irbesartan-treated patients (p<0.0001). Per request from the FDA, the efficacy data contained in the FDA-approved label is a post-hoc sensitivity analysis that evaluates the first 281 randomized patients, a subset of the full trial population. The mean reduction in proteinuria from baseline in the post-hoc sensitivity analysis is 45% for FILSPARI versus 15% for the active control, irbesartan. Both the pre-specified and post-hoc sensitivity analyses have demonstrated that FILSPARI achieves a rapid and sustained reduction in proteinuria, with statistically significant and clinically meaningful improvement compared to the active comparator irbesartan. Per the study protocol, patients continue in a blinded manner in the PROTECT Study to fully assess the treatment effect on eGFR slope over 110 weeks in the confirmatory endpoint analysis. Results from the confirmatory endpoint analysis are expected in the fourth quarter of 2023.
Results from the interim assessment in the PROTECT Study showed that FILSPARI was well tolerated with a clearly defined safety profile that has been consistent across all clinical trials conducted to date. In PROTECT, the most common adverse reactions (≥ 5%) are peripheral edema, hypotension (including orthostatic hypotension), dizziness, hyperkalemia, and anemia. Because of the risks of liver injury and birth defects, FILSPARI is available only through a Risk Evaluation and Mitigation Strategy (REMS) approved by the FDA.
Bonnie Schneider, executive director and co-founder of the IgA Nephropathy Foundation said, “For decades people living with IgA nephropathy have had limited treatment options while facing a progression toward kidney failure. Today is a day of celebration for the RKD community, for our patients, and their families.”
"IgA nephropathy is associated with depression, fatigue, loss of social and work opportunities and anxiety about the need for dialysis or transplant. The disease often manifests in adults in their 20s or 30s – a time when people are focused on building livelihoods and families,” said Kelly Helm, executive director of patient engagement at NephCure. “We are thrilled that today's FDA accelerated approval of FILSPARI brings forward a new and innovative treatment option for many people living with IgA nephropathy.”
Travere Therapeutics has established Travere TotalCareTM to provide a comprehensive patient support program to enable a smooth experience for patients, their caregivers and healthcare providers. This program provides services, assistance and resources that will help patients understand IgAN, manage the insurance process, fill their prescriptions and initiate treatment.
About FILSPARI (sparsentan)
FILSPARI (sparsentan) is a once-daily, oral medication designed to selectively target two critical pathways in the disease progression of IgAN (endothelin-1 and angiotensin II) and is the first and only non-immunosuppressive therapy approved for the treatment of this condition. FILSPARI is a prescription medicine indicated to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a UPCR ≥1.5 g/g.
20 February 2023
